Product name: Theaflavin-3'-gallate
Synonym name: 3′-O-(3,4,5-Trihydroxybenzoyl)
Catalogue No.: BP1386
Cas No.: 28543-07-9
Formula: C₃₆H₂₈O₁₆
Mol Weight: 716.604
Botanical Source: Black Tea
Physical Description:
Type of Compound: Polyphenols

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle

Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.

The product could be supplied from milligrams to grams
Inquire for bulk scale.

​Description:

Theaflavin-3'-gallate, acts as prooxidants and induces oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.

References:

Basic Clin Pharmacol Toxicol. 2008 Jul;103(1):66-74.    

Theaflavin-3-gallate and theaflavin-3'-gallate, polyphenols in black tea with prooxidant properties.   

This study compared the in vitro responses of human gingival fibroblasts and of carcinoma cells derived from the tongue to theaflavin-3-gallate (TF-2A) and Theaflavin-3'-gallate (TF-2B), polyphenols in black tea. 

METHODS AND RESULTS:

In a cell-free assay, TF-2A and Theaflavin-3'-gallate reacted directly with reduced glutathione (GSH), in a time- and concentration-dependent manner. Intracellular storages of GSH were depleted on treatment of the cells with the theaflavin monomers. Depletion of intracellular GSH was more extensive with TF-2A than with Theaflavin-3'-gallate and was more pronounced in the carcinoma, than in the normal, cells. The toxicities of the theaflavins were potentiated when the cells were cotreated with the GSH depleter, d,l-buthionine-[S,R]-sulfoximine. In the presence of catalase, pyruvate and divalent cobalt, all scavengers of reactive oxygen species, the cytotoxicities of the theaflavins were lessened. TF-2A and Theaflavin-3'-gallate induced lipid peroxidation in the carcinoma cells, whereas in the fibroblasts, peroxidation was evident upon exposure to TF-2A, but not to Theaflavin-3'-gallate. 

CONCLUSIONS:

These studies demonstrated that the black tea theaflavin monomers, TF-2A and Theaflavin-3'-gallate, act as prooxidants and induce oxidative stress, with carcinoma cells more sensitive than normal fibroblasts.    

HPLC of Theaflavin-3'-gallate

HNMR of Theaflavin-3'-gallate

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Theaflavin-3'-gallate (TF3'G) is an important class of natural polyphenolic compounds belonging to the Theaflavins family, widely found in fermented teas, especially black tea. As one of the main bioactive components in tea, TF3'G has attracted widespread attention in the field of natural product pharmacology in recent years due to its unique chemical structure and diverse bioactivity. Its potential roles in the prevention and treatment of various diseases, including antioxidant, anti-inflammatory, anti-tumor, and cardiovascular protection, provide a rich research foundation for the development of natural medicines.

This paper systematically reviews the chemical structure and physicochemical properties of TF3'G, plant origin and extraction methods, pharmacological activity, mechanism of action and molecular targets, druggability evaluation, and pharmacokinetic characteristics. Combining current clinical application prospects and future research directions, it aims to provide comprehensive and in-depth reference materials for researchers in natural product pharmacology and related fields.

Chemical structure and physicochemical properties

TF3'G has the molecular formula C37H30O16, molecular weight 716.6040, and CAS number 28543-07-9. Its structure belongs to theaflavin compounds, formed by the ester bond of catechins and gallic acid to form a complex polyphenol. The core structure of TF3'G contains a flavonoid dimeric framework, with the 3' hydroxyl group esterified by gallate, giving it unique chemical properties and biological activity.

In terms of physicochemical properties, TF3'G has a LogP value of 2.1042, indicating moderate lipid solubility, which facilitates cell membrane penetration; TPSA (Topological Polar Surface Area) is 284.3600. The higher polar surface area suggests better solubility in polar environments, but lower water solubility (0.0402), which may limit its oral bioavailability. The blood-brain barrier penetration ability is low, indicating limited function in the central nervous system. The hERG suppression test results were negative, indicating that TF3'G carries a low risk of toxicity to cardiac potassium channels. The Ames test result was 0.6, indicating a low genotoxicity risk.

Plant Origins and Extraction Methods

TF3'G is mainly found in fermented tea leaves, especially in black tea (Camellia sinensis), a theaflavin compound formed by the oxidation and polymerization of catechins during the fermentation process. The fermentation process of tea catalyzes the oxidation of catechins through polyphenol oxidase (PPO) and peroxidase (POD), producing various theaflavin derivatives including TF3'G.

The main methods for extracting TF3'G include solvent extraction, liquid chromatography separation, and purification techniques. Common solvents include ethanol, water, methanol, etc., combined with ultrasound-assisted extraction or heating reflux to improve extraction efficiency. Subsequently, separation and purification are performed by high-performance liquid chromatography (HPLC) or preparative HPLC to ensure the purity and activity of the compounds. In recent years, supercritical fluid extraction (SFE) and membrane separation technologies have also been applied to extract theaflavin compounds, enhancing the feasibility of industrial production.

Pharmacological activity research

Antioxidant activity

TF3'G, as a natural polyphenol product, has significant antioxidant capacity. They can effectively scavenge free radicals, such as hydroxyl radicals (· OH), superoxide anion (O2·-), and hydrogen peroxide (H2O2) to reduce cellular damage caused by oxidative stress. In vitro DPPH radical scavenging experiments and cell models have confirmed its excellent antioxidant performance.

Anti-inflammatory effects

Multiple studies have shown that TF3'G can significantly inhibit the expression of inflammatory factors, including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and nitric oxide synthase (iNOS). By modulating the NF-κB signaling pathway, it suppresses inflammatory responses and reduces tissue damage, demonstrating potential anti-inflammatory therapeutic value.

Antitumor activity

TF3'G demonstrates the ability to inhibit cell proliferation, induce apoptosis, and block the cell cycle across various tumor cell lines. Its mechanism of action involves regulating multiple signaling pathways, such as PI3K/Akt, MAPK, and p53 pathways, promoting programmed death of cancer cells and inhibiting tumor invasion and metastasis.

Cardiovascular protection

TF3'G improves vascular endothelial function through antioxidant and anti-inflammatory effects, reduces ox-LDL oxidation of low-density lipoprotein (ox-LDL), and prevents atherosclerosis. In addition, its inhibitory effect on platelet aggregation also helps prevent thrombosis, demonstrating good cardiovascular protective potential.

Other pharmacological effects

TF3'G also exhibits multiple biological activities, including antibacterial, antiviral, neuroprotection, and regulation of glycolipid metabolism, providing a theoretical basis for its application in the prevention and treatment of various diseases.

Mechanism of action and molecular targets

The pharmacological effects of TF3'G are mainly realized through multiple targets and multiple pathways. Its key molecular targets include:

• NF-κB signaling pathway: TF3'G inhibits the phosphorylation and degradation of IκBα, blocks NF-κB nuclear translocation, and reduces inflammatory factor expression.
• PI3K/Akt pathway: regulates cell survival and apoptosis. TF3'G promotes tumor cell apoptosis by inhibiting this pathway.
• MAPK pathway: Affects cell proliferation and stress responses; TF3'G regulates cell fate by regulating ERK, JNK, and p38 kinase activities.
• Antioxidant enzyme system: activates the Nrf2/ARE signaling pathway, enhances the activity of endogenous antioxidant enzymes (such as SOD, CAT, GPx), and improves cellular antioxidant defense.
• Platelet-activating factor (PAF) receptor: Inhibits platelet aggregation and prevents thrombosis.

Additionally, TF3'G influences cell metabolism and proliferation by regulating mitochondrial function, calcium homeostasis, and cyclin expression, demonstrating its multidimensional pharmacological regulatory capabilities.

Druggability evaluation and pharmacokinetics

The druggability parameters of TF3'G indicate that it has certain development potential. Although the molecular weight of 716.6 is relatively large, the LogP 2.1 is moderate, which facilitates membrane penetration. A higher TPSA and lower water solubility suggest that oral absorption may be limited, requiring pharmacological approaches to improve bioavailability. The blood-brain barrier penetration ability is low, limiting its application in central nervous system diseases but reducing the risk of CN toxicity.

Negative hERG channel suppression indicates good cardiac safety, and Ames test results indicate low genotoxicity risk and meet safety requirements. Pharmacokinetic studies show that TF3'G is metabolized stably in the body, mainly through hepatic enzyme systems, with most metabolites being water-soluble conjugates that facilitate excretion. Its half-life is moderate, with a certain duration in the body.

To address the pharmacokinetic bottleneck of TF3'G, strategies such as nanocarriers, liposomal encapsulation, and structural modification have been proposed to improve its bioavailability and targetability.

Prospects and outlooks for clinical applications

Thanks to its rich pharmacological activity and good safety, TF3'G demonstrates broad clinical application potential in the prevention and treatment of various diseases. Its antioxidant and anti-inflammatory effects offer new therapeutic approaches for chronic inflammatory diseases such as atherosclerosis, diabetes, and chronic arthritis. Its antitumor activity makes it a strong candidate for adjuvant therapy, especially in combination chemotherapy and radiotherapy, where synergistic effects may be achieved.

Although there are currently no large-scale clinical trial reports, TF3'G's natural origin and low toxicity lay the foundation for its clinical translation. Future research should focus on optimizing pharmacokinetics, developing dosage forms, and deeply analyzing mechanisms to promote their transition from laboratory research to clinical application.

In addition, combining modern drug design technologies, such as computer-aided drug design (CADD), high-throughput screening, and multi-omics analysis, will help discover new targets and indications for TF3' + N'G, expanding its application areas.

Conclusion

Theaflavin-3'-gallate, an important natural polyphenolic compound in tea, demonstrates broad research and application prospects in fields such as antioxidant, anti-inflammatory, anti-tumor, and cardiovascular protection due to its unique chemical structure and diverse biological activities. Its excellent safety and druggability parameters provide a solid foundation for drug development.

In the future, combining modern drug development technologies, in-depth exploration of its mechanisms of action, optimization of pharmacokinetic properties, and systematic clinical studies will help promote TF3'G to become an important member of new natural medicines and contribute more value to human health.